3-amino-4-dihalo pyrazolones

ABSTRACT

3-AMINO-4,4-DIHALO-5-PYRAZOLONES OF THE FORMULA   1-Y,3-(R-N(-R1)-),4-X,4-X&#39;&#39;,5-(O=)-2-PYRAZOLINE   WHEREIN X AND X&#39;&#39; ARE SELECTED FRO THE GROUP CONSISTING OF CHLORINE AND BROMINE, Y IS SELECTED FROM THE GROUP CONSISTING OF ALKYL, CYCLOALKYL, AND ARYL WHICH MAY BE SUBSTITUTED AND R AND R1 ARE SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, ALKYL, ARYL, CYCLOALKYL AND ARALKYL WHICH POSSES; FUNGICIDAL ACTIVITY AND THEIR PREPARATION.

United States Patent 4 rm. (:1. (367d 49/06 U.S. Cl. 260-310 A 8 ClaimsABSTRACT OF THE DISCLOSURE 3-amino-4,4-dihalo-S-pyrazolones of theformula wherein X and X are selected from the group consisting ofchlorine and bromine, Y is selected from the group consisting of alkyl,cycloalkyl and aryl which may be substituted and R and R are selectedfrom the group consisting of hydrogen, alkyl, aryl, cycloalkyl andaralkyl which possess fungicidal activity and their preparation.

OBJECTS OF THE INVENTION The novel 3-amino'4,4-dihalo-5-pyrazolones ofthe in vention have the formula R1 R N x c l X fi wherein X and X areselected from the group consisting of chlorine and bromine, Y isselected from the group consisting of alkyl, cycloalkyl and aryl whichmay be substituted and R and R are selected from the group consisting ofhydrogen, alkyl, aryl, cycloalkyl and aralkyl.

Preferably Y is alkyl of 1 to 7 carbon atoms, cycloalkyl of 5 to 7carbon atoms or monocyclic aryl, all of which may be substituted with atleast one member of the group consisting of halogen, lower alkyl andlower alkoxy of 1 to 7 carbon atoms, trifluorornethyl, nitro and aminoand R and R are hydrogen, alkyl of 1 to 7 carbon atoms, cycloalkyl of 5to 7 carbon atoms, monocyclic aralkyl having 1 to 7 alkyl carbon atomsand monocyclic aryl. Particularly interesting compounds are1-(4'-chlorophenyl)-3'amino-4,4'-dichloro-S-pyrazolone and1-(3trifluoromethylphenyl) -3-amino-4,4-d ichloro-S-pyrazolone.

Patented Jan. 41, 1972 The novel pyrazolones of Formula I possess avaluable anti-fungal activity which makes them particularly suitable foruse in the agricultural field for disinfecting soils and protectingseeds.

The process of the invention for the preparation of the pyrazolones ofFormula I comprises condensing a lower alkyl cyanacetate of the formulai N C-CHr-C-O Alk (11) wherein Alk is lower alkyl in the presence of abasic agent with a hydrazine of the formula YNHNH wherein Y has theabove definition to form a pyrazolone of the formula (IVa) reacting ifdesired the latter compound with an amine selected from the groupconsisting of a primary amine and a secondary amine in the presence ofan acid agent, and reacting a pyrazolone of the formula (IVb) wherein Rand R have the above definitions with a chlorinating or brominatingagent to form the 3-amino-4,4- dihalo-S-pyrazolone of Formula I.

The lower alkyl cyanacetate is preferably methyl or ethyl cyanacetateand the basic agent is preferably an alkali metal alcoholate such aspotassium or sodium methylate or ethylate in excess alcohol. The acidagent is preferably an organic acid such as acetic acid or propionicacid. The halogenating agent is preferably chlorine or bromine in aninert organic solvent such as carbon tetrachloride or carbon sulfide.

The fungicidal compositions of the invention are comprised of aneffective amount of at least one compound of Formula I and a majoramount of an inert agricultural carrier. The compositions may be in theform of emulsions, solutions, suspensions, concentrates, wettablepowders, dusts, etc.

The novel method of the invention for controlling fungi comprisescontacting the fungi with an effective amount of at least one pyrazoloneof Formula I. The compounds are preferably incorporated in the soil orseeds are treated by the said compound.

In the following examples there are described several preferredembodiments to illustrate the invention. However, it should beunderstood that the invention is not intended to be limited to thespecific embodiments.

Example I.Preparation of 1-phenyl-3-amino-4,4- dichloro-S-pyrazoloneStep A: 1-phenyl-3-amino-5-pyraZolone.-46 g. of sodium were introducedin small amounts into 900 cc. of ethanol and after the solution obtainedwas cooled, 113 g. of ethyl cyanacetate and 108 g. of phenylhydrazinewere added thereto. The mixture was agitated for an hour and then heatedat reflux for fifteen hours. Ethanol was eliminated by distillation invacuo and water was added to the residue. The aqueous phase was washedwith ether, acidified by addition of acetic acid and cooled Theprecipitate thus formed was recovered by suction-filtration, washed anddried to obtain 88 g. of 1-phenyl-3-amino-5- pyrazolone having a meltingpoint of 220-221 C.

Step B: 1-pheny1-3-amino-4,4-dichloro-5-pyrazolone.-- 20 g. of1-phenyl-3-amino-5-pyrazolone was added into 400 cc. of carbontetrachloride and the suspension was cooled to C. In about 15 minutes,at 0 C., 105 cc. of a solution of 16 g. of chlorine per 100 cc. ofcarbon tetrachloride was added thereto and the mixture was agitated for30 minutes at C. The precipitate thus formed was vacuum filtered, washedand dried to obtain 24 g. of l-phenyl-3-amino-4,4-dichloro-S-pyrazolonehaving a melting point of 147148 C.

A sample of the product was purified by crystallization from isopropylether and had a melting point of 148- 149 C.

AnaIysis.C H Cl N O; molecular weight=244.l. Calculated (percent):C,44.28; H, 2.89; Cl, 29.05; N, 17.21. Found (percent): C, 44.4; H, 3.2;Cl, 29.2; N, 17.0.

As far as is known, this compound is not described in the literature.

Example II.--Preparation of 1-(4'-chlorophenyl)-3-amino-4,4-dichloro-5-pyrazolone Step A:l-(4'-chlorophenyl)-3-amino-5-pyrazolone.- 16.5 g. of sodium were addedin small amounts to 450 cc. of ethanol under an atmosphere of nitrogen.When dissolution of the sodium was complete, the reaction mixture wascooled to ambient temperature and 43 g. of ethyl cyanacetate and 51 g.of 4-chlorophenylhydrazine were added thereto. The reaction mixture wasstirred for one hour at ambient temperature and then for fifteen hoursat reflux. After cooling the reaction mixture, it was concentrated todryness under reduced pressure. Water was added to the residue and theaqueous solution was washed with ether, acidified with acetic acid andcooled. The precipitate was recovered by suction-filtration and waswashed with water and dried to obtain 40 g. of 1-(4-chlorophenyl)-3-arnino-5-pyrazolone having a melting point of 173-174C.

A sample of this product upon crystallization had a melting point of173-174 C.

Analysis.C H ClN O; molecular Weight=209.6. Calculated (percent): C,51.56; H, 3.84; Cl, 16.91; N, 20.05. Found (percent): C, 51.7; H, 4.1;Cl, 16.7; N, 19.7.

Step B: 1-(4'-chlorophenyl)-3-amino-4,4-dichloro-5- pyrazolone.21 g. of1-(4'-chlorophenyl)-3-amino-5- pyrazolone were added to 400 cc. ofcarbon tetrachloride and the reaction mixture was cooled to 0 C. Overabout minutes, 85 cc. of a solution of 18 g. of chlorine in 100 cc. ofcarbon tetrachloride was added thereto and the mixture was agitated for30 minutes at 20 C. The precipitate was vacuum filtered, washed withcarbon tetrachloride and dried to obtain 24 g. of 1-(4'-chlorophenyl)- 3amino 4,4 dichloro 5 pyrazolone with a melting point of 158-159 C.

A sample of this product upon crystallization from methanol had anunchanged melting point.

Analysis.C H Cl N O, molecular weight=278.5. Calculated (percent): C,38.81; H, 2.17; Cl, 38.19; N, 15.09. Found (percent): C, 38.8; H, 2.3;Cl, 37.9; N, 15.1.

As far as is known, this compound is not described in the literature.

Example II.--Preparation of 1-(3',4-dichlorophenyl)-3-amino-4,4-dichloro-5-pyrazolone Step A: 1 (3,4' dichlorophenyl) 3amino 5- pyrazolone.In a manner analogous to that of Example I,3,4-dichlorophenylhydrazine and ethyl cyanacetate were condensed toobtain 1 (3,4 dichlorophenyl) 3- amino-S-pyrazolone with a melting pointof 239240 C.

AnaIysis.C H Cl N O; molecular weight=244.1. Calculated (percent): C,44.28; H, 2.90; CI, 29.05; N, 17.21. Found (percent): C, 44.5; H, 3.3;Cl, 28.9; N, 17.2.

As far as is known, this compound is not described in the literature.

Step B: 1 (3,4' dichlorophenyl) 3 amino 4,4- dichloro-S-pyrazolone.-In amanner analogous to that of Example I, chlorine in solution in carbontetrachloride was reacted with 1 (3',4 dichlorophenyl) 3 amino-S-pyra-zolone to obtain 1 (3',4 dichlorophenyl)-3- amino 4,4 dichloro 5pyrazolone with a melting point of 129130 C.

Analysis.C H C1 N O; molecular weight=313.0. Calculated (percent): C,34.53; H, 1.61; CI, 45.32; N, 13.42. Found (percent): C, 34.5; H, 1.7;Cl, 45.0; N, 13.2.

As far as is known, this compound is not described in the literature.

Example IV.-Preparation of 1-(4'-methoxyphenyl)- 3-amino-4,4-dichloro-5-pyrazolone Step A: 1- (4-methoxyphenyl)-3-amino-5-pyrazolone.- In a manner analogous to that of Example I,4-methoxyphenylhydrazine was condensed with ethyl cyanacetate to obtain1-(4-methoxyphenyl)-3-amino-5-pyra-zolone with a melting point of l89190C.

Step B: 1-(4-rnethoxyphenyl)-3-amino-4,4-dichloro-5- pyrazolone.In amanner analogous to that of Example I,1-(4'-methoxyphenyl)-3-amino-5-pyrazolone was chlorinated to obtain1-(4-methoxyphenyl)-3-amino-4,4-dichloro-S-pyrazolone with a meltingpoint of 17017l C.

Analysis. C -H Clg-N O molecular weight=274.1. Calculated (percent): C,43.81; H, 3.31; CI, 25.87; N, 15.33. Found (percent): C, 43.9; H, 3.7;Cl, 25.7; N, 15.2.

As far as is known, this compound is not described in the literature.

Example V.Preparation of 1-(3-chloro-4'-methoxyphenyl)-3-amino-4,4-dichloro-5-pyrazolone Step A: l (3chloro-4-methoxyphenyl)-3-amino-5- pyrazolone. In a manner analogous tothat of Example I, 3-chloro-4-methoxyphenylhydrazine was condensed withethyl cyanacetate to obtain1-(3'-chloro-4-methoxy-phenyl)-3-amino-5-pyrazolone having a meltingpoint of 229- 230 C.

Analysis.C H ClN O molecular weight=239.6. Calculated (percent): C,50.12; H, 4.20; Cl, 14.79; N, 17.54. Found (percent): 50.4; H, 4.4; Cl,14.9; N, 17.6.

As far as is known, this compound is not described in the literature.

Step B: 1-(3-chloro-4-methoxyphenyl)-3-amino-4,4-dichloro-5-pyrazolone.-In a manner analogous to that of Example I, 1 (3'chloro-4'-methoxyphenyl)-3-amino-5- pyrazolone was chlorinated to form1-(3'-chloro-4'-methoxyphenyl) 3 amino 4,4-dichloro-5-pyrazolone with amelting point of 202-203 C.

Analysis.C H Cl N O' molecular weight=308.5. Calculated (percent): C,38.93; H, 2.61; Cl, 34.48; N, 13.62. Found (percent): C, 38.8; H, 2.7;CI, 34.6; N, 13.9.

As far as is known, this compound is not described in the literature.

The starting product, 3-chloro-4-methoxyphenyl-hydrazine, was preparedas follows:

(a) Diazotation.-20 g. of 3-chloro-4-methoxyaniline were introduced into150 cc. of aqueous solution of 22 B. hydrochloric acid and the reactionmixture was heated to 70 C. After cooling to 0 C., a solution of 17 g.of sodium nitrite in 200 cc. of water was added thereto in about 30minutes and the mixture was stirred one hour at 0 C.

(b) Reduction.--Into the reaction mixture obtained above, 56 g. ofdihydrated stannous chloride in solution in cc. of aqueous solution of22 B. hydrochloric acid were introduced and the mixture was stirred fortwo hours at 0 C. The precipitate thus formed was recovered byfiltration.

(c) 3 chloro 4-methoxyphenyl-hydrazine-hydrochloride.The crude productobtained in (b) was introduced over about 30 minutes at C. into 200 cc.of 4.15 N aqueous solution of potassium hydroxide. The mixture wasagitated at 0 C. for thirty minutes. The precipitate thus formed wasrecovered by vacuum filtration, was washed with Water, dried and addedto 300 cc. of ethanol. The solution thus obtained was cooled to 0 C. andhydrochloric gas was bubbled into it until precipitation stopped. Theprecipitate thus formed was recovered by vacuum filtration and waswashed with ether and dried to obtain 15 g. of the hydrochloride of3-chloro-4-methoxyphenylhydrazine having a melting point of 250 C.

(d) Obtaining 3 chloro-4-methoxyphenylhydrazine.-- The 15 g. ofhydrochloride obtained in (c) was added to 450 cc. of water. Thesolution was made alkaline with sodium hydroxide and was extracted withether. The ethereal extracts were washed with water, dried andconcentrated to dryness under reduced pressure to obtain 9 g. of 3chloro 4 methoxyphenylhydrazine with a melting point of 68 C., which wasused preferably without delay, to avoid a possible alteration.

As far as is known, the hydrochloride of 3-chloro-4-methoxyphenylhydrazine, and 3-chloro-4-methoxyphenylhydrazine, are notdescribed in the literature.

Example VI.-Preparation of l-phenyl-3-methylamino-4,4-dichloro-5-pyrazolone Step A: 1 phenyl3-methylamino-5-pyrazolone.-400 cc. of acetic acid were introduced inabout an hour at -50 C. into 100 g. of methylamine and after raising thetemperature of the reaction mixture to 20 C., 60 g. of1-phenyl-3-amino-S-pyrazolone were added thereto and the reactionmixture was heated to reflux which was maintained for fourteen hours.After cooling the reaction mixture was poured into water, the insolublematter formed was eliminated by filtration. The filtrate was adjusted topH of 7 by adding thereto an aqueous solution of sodium bicarbonate. Theaqueous phase was extracted with methylene chloride and the methylenechloride extracts were washed with water, dried and concentrated todryness. The residue was dissolved in methanol, the precipitate thusformed was vacuum filtered to obtain 20 g. of l-phenyl-3-methylamino-S-pyrazolone with a melting point of 164- 165 C. A sample ofthis product upon recrystallization from methanol had a melting point of166-167 C.

Analysis.C H N O; molecular weight:189.2. Calculated (percent): C,63.47; H, 5.86; N, 22.21. Found (percent): C, 63. 8; H, 6.0; N, 22.1.

Stage C: 1-phenyl-3-rnethylamino-4,4dichloro-5-pyrazolone.20 g. of 1phenyl 3-methylamino-S-pyrazolone were dissolved in 350 cc. ofchloroform and the solution obtained was cooled to 0 C. At thistemperature over about 20 minutes, 100 cc. of solution of g. of chlorinein 100 cc. of carbon tetrachloride was added. The mixture was agitatedat 0 C. for thirty minutes, then concentrated to a small volume underreduced pressure. After cooling, the precipitate thus formed was vacuumfiltered, washed and dried to obtain 23 g. of1-phenyl-3-methylamino-4,4- dichloro-S-pyrazolone with a melting pointof 14ll42 C. A sample of this product upon recrystallization fromisopropyl ether had a melting point of 141l42 C.

Analysr's.C H Cl N O; molecular weight=258.l. Calculated (percent): C,46.53; H, 3.52; Cl, 27.47; N, 16.28. Found (percent): C, 46.4; H, 3.7;Cl, 27.2; N, 16.1.

As far as is known, this compound is not described in the literature.

Example VII.-Preparation of1-phenyl-3-dimethylamino-4,4-dichloro-S-pyrazolone In a manner analogousto that of Example VI, 1-phenyl- 3-amino-5-pyrazolone was condensed inan acetic acid medium with dimethylamine to obtain1-phenyl-3-dimethylaminopyrazolone having a melting point of 139- 140 C.The chlorination of this compound gave l-phenyl- 63-dimethylamino-4,4-dichloro-5-pyrazolone melting at 94- 95 C.

Analysis.-C H Cl N O; molecular weight=272.1. Calculated (percent): C,48.55; H, 4.07; CI, 26.06; N, 15.45. Found (percent): C, 48.8; H, 4.1;Cl, 26.1; N, 15.1.

As far as is known, 1-phenyl-3-dimethylamino-4,4-dichloro-5-pyrazoloneis not described in the literature.

Example VIII.-Preparation of1-phenyl-3-benzylamino-4,4-dichloro-5-pyrazolone In a manner analogousto that of Example VI, l-phenyl- 3-amino-5-pyrazolone was condensed inan acetic acid medium with benzylamine to obtainl-phenyl-3benzylamino-S-pyrazolone melting at 132-133 C. Thechlorination of this compound gave 1-phenyl-3-benzylamino-4,4-dichloro-S-pyrazolone melting at 'l83184 C.

Analysis.-C H Cl N O; molecular weight=334.2. Calculated (percent): C,57.49; H, 3.92; Cl, 21.22; N, 12.57. Found (percent): C, 57.5; H, 4.1;Cl, 21.0; N, 12.7.

As far as is known, this compound is not described in the literature.

Example IX.Preparation of 1-(3'-trifiuoromethylphenyl-3-amino-4,4-dichloro-5-pyrazolone 19 g. of 1-(3-trifluoromet hylphenyl)3 amino-5- pyrazolone were added to 250 cc. of chloroform and thereaction suspension was cooled to 0 C. Over a few minutes, a solution of11 g. of chlorine in cc. of carbon tetrachloride was added thereto andagitated for one hour at 0 C. The solvent was eliminated by distillationunder reduced pressure and to the residue was added 50 cc. of isopropylether and 50 cc. of petroleum ether (B.P. 6080 C.). The solution wascooled to 0 and the precipitate thus formed was filtered and dried toobtain 19 g. of 1-(3trifiuoromethylphenyl)-3-amino 4,4 dichloro-S-pyrazolone, melting at 100 C. A sample of this product wasrecrystallized from a mixture of isopropyl ether and petroleum ether(B.P. 60-80 C.).

Analysis.C H Cl F N O; molecular weight=312.078. Calculated (percent):C, 38.48; H, 1.93; Cl, 22.75; F, 18.26; N, 13.46. Found (percent): C,38.6; H, 2.3; Cl, 22.4; F, 18.4; N, 13.6.

As far as is known, this compound is not described in the literature.

1-(3-trifiuoromethylphenyl) 3 amino-S-pyrazolone can be prepared asfollows:

13.8 g. of sodium cut into fragments were added to 600 cc. of ethanoland the mixture was agitated until total dissolution occurred. Thetemperature of the reaction mixture was raised to 20 C. and over a fewminutes 34 g. of ethyl cyanacetate, then 53 g. ofmeta-trifluoromethylphenylhydrazine (obtained according to the processof E. J. Forbes et al., Tetrahedron, vol. 8, p. 67 (1960)) were addedthereto. The reaction mixture was heated to reflux and maintained therefor 16 hours. The ethanol was eliminated by distillation under reducedpressure and the residue was admixed with water. The solution thusobtained was extracted with ethyl ether. The aqueous phase was madeacidic with acetic acid. The precipitate thus formed was vacuumfiltered, washed with water and dried. The product thus obtained wasdissolved in ethyl ether and the ethereal solution was extracted with anN aqueous solution of hydrochloric acid, then with water, dried andconcentrated to dryness by distillation under reduced pressure. Theresidue was dissolved in isoproppl ether, which was cooled. Theprecipitate thus formed was vacuum-iiltered, and dried to obtain 19 g.of 1-(3-trifluoromethylp'henyl)-3-amino-5-pyrazolone, melting at 159 C.A sample of this product upon crystallization from ethanol melted at 160C.

Analysis.-C H F N O; molecular weight=243.l8. Calculated (percent): C,49.38; H, 3.31; F, 23.44; N, 17.28. Found (percent): C, 49.6; H, 3.5; F,23.3; N, 17.4.

As far as is known, this compound is not described in the literature.

Example X.Fungicidal activity of 1-(4'-chlorophenyl)-3-amino-4,4-dichloro-S-pyrazolone (compound A) (A) Activity on F usariumroseum on wheat).The effectiveness of compound A was studied on seeds ofwheat contaminated with spores of Fusarium roseum and then treated.

Contamination of the Champlain wheat was effected by steeping the seedsin a suspension of spores of Fusarium roseum adjusted to 100,000 sporesper cc. and then the seeds were dried for 24 hours in the ambient air.The seeds were then treated with a quantity of compound A correspondingto 80 g./quintal. The sowing was effected on dishes of sand. There wereplots of 100 grains each. After 4 weeks storage at 20 C., the number ofhealthy, diseased and dead plants were ascertained.

The results are given in percentage eflectiveness, taking account ofparallel tests with a non-treated control. In

these conditions at the dose of 80g./quintal, the percentageeffectiveness observed was 61%.

(B) Activity on Rhizoctonia solani.-- The eflFectiveness of compound Awas determined by sowing test-plants in contaminated soil then treated.A mixture consisting of earth sand and /3 Polish peat was used as soiland 1 volume of culture of Rhizoctonia solani (on bran and vermiculiteenriched with Kn-opp liquid) was added to 29 volumes of soil. Thetreatments were effected by direct incorporation of compound A in thesoil at doses of 500 and 250 p.p.m. of active material and then the soilwas left at rest for three weeks. The test plant used was Phaseolusaureus Mungo and the treated soil was distributed into the potscontaining the test plant; there were 5 pots, each containing 10test-plants, per concentration.

After 12 days storage at 20 C., the healthy plants were counted and theresults were expressed in percentage of eifectiveness taking account ofa non-treated oontrol plant. In these conditions the percentage ofeffectiveness for compound A was 87% at the concentration of 500 p.p.m.and 31% at the concentr-ation of 0 p.p.m.

Various modifications of the compositions and method of the inventionmay be made without departing from the spirit or scope thereof.

We claim:

1. 1-(4'-chlorophenyl) 3 amino 4,4 dichloro-S- pyrazolone.

2. l-(3,4'-dichlorophenyl) 3 amino-4,4-dichloro-5- pyrazolone.

3. 1-(4'-rnethoxyphenyl) 3 "amino 4,4 dichloro-S- pyrazolone.

4. 1-(3-chloro-4'-methoxyphenyl) 3 amino-4,4-dichloro-S-pyrazolone.

5. 1-phenyl-3-methylamino-4,4-dichloro-S-pyrazolone.

6. 1-phenyl-3-dimethylamino-4,4-dichloro-5-pyrazolone.

7. 1-phenyl-3-benzylamino-4,4-dichloro-5-pyrazolone.

8. 1 (3' trifluoromethylphenyl) 3 amino-4,4-dichloro-5-pyrazolone.

References Cited UNITED STATES PATENTS 2,899,443 8/1959 Schulze 260-3103,006,759 10/1961 Loria et a1. 260-3l0 FOREIGN PATENTS 1,069,534 5/1967Great Britain 260-310 OTHER REFERENCES Elderfield: HeterocyclicCompounds, vol. 5, p. 151, NY. Wiley, 1957.

Gagnon et al.: Canadian J. Res., vol. 27-B, pp. 204 (1949) Hull: J.Chem. Soc. (London), 1967, Sec. 0., pp. 1154-5.

Netherlands application 6707544, November 1967 (21 pages spec.).

Weiss'berger et al.: J. Amer. Chem. Soc., vol. 64, pp. 2133-6 (1942).

Weissberger et al.: J. Amer. Chem. Soc., vol. 66, pp. 1849-51 (1944).

Westtiti: Aeta Chem. Scand, vol. 6, Pt. 2, pp. 1499- 1515 (1952).

Wiley et al.: Pyrazolones, Pyrazolidines, and Derivatives (v01. 20-TheChemistry of Heterocyclic Compounds.

Weissberger, ed.) pp. 81-3 and 344-5, N.Y. Interscience,

Wiley, 1964.

NATALIE TROUSOF, Primary Examiner U.S. Cl. X.R.

